Project Summary This project?s objective is to develop a sprayable, biodegradable polymer surgical sealant for decreasing high mortality rate complications that occur after surgery. Surgical sealants currently available in the clinic have high cost, poor material properties, and are difficult to precisely deposit. Utilizing a technique called solution blow spinning, we have demonstrated the ability to directly deposit conformal biodegradable polymer fiber surgical sealants to the site of surgery in vivo with exceptional sealing strength. The overall hypothesis for this research is that reducing inflammation and increasing tissue adhesion of polymer surgical sealants will allow us to demonstrate success in pre-clinical trials for reducing complication rate after an intestinal anastomosis. This project will investigate sprayable combinations of biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) or poly(lactide-co-caprolactone), poly(ethylene glycol) (PEG), and functionalized nanoparticles that can reduce inflammation or increase wet tissue adhesion. The Specific Aims of the proposed research are: (1) Reduce inflammation in response to biodegradable polymers by controlling hydrophilicity using block copolymer additives. (2) Evaluate intestinal function and complication rate for PLGA-PEG surgical sealants in vivo. (3) Increase wet tissue adhesion using functionalized nanoparticles that increase physical bonding at the interface. The insights produced by these studies will also be applicable to other polymeric biomedical devices, such as sutures and tissue engineering scaffolds, increasing the significance of the work. This proposal has been designed to complement a fellowship training plan that develops cross-disciplinary technical skills in materials science and biology, leading to an academic career path in biomaterials research.